Internal Medicine

Targeted cancer therapy with tyrosine kinase inhibitors

Synonyms

The tyrosine kinase inhibitors include:
Imatinib, Sunitinib, Midostaurin and many more

introduction

Tyrosine kinase inhibitors are also known as tyrosine kinase inhibitors. It is a group of medicines used to inhibit the enzyme tyrosine kinase, which is involved in the development, survival and spread of cancer in the body. Tyrosine kinase inhibitors, such as the active ingredients imatinib, sunitinib and others, are used in the treatment of various tumor diseases, for example chronic myeloid leukemia (CML), certain types of lung cancer (non-small cell lung cancer) or renal cell carcinoma.

If you are interested in classic chemotherapy, we recommend our main page: chemotherapy

Indications for tyrosine kinase inhibitors

The commercially available tyrosine kinase inhibitors are used for various diseases, mainly cancer, but also for rheumatoid arthritis. The latter is an inflammatory disease of the joints, which initially affects the finger and toe joints. The indications for tyrosine kinase inhibitors include:

chronic myeloid leukemia, a disease of the white blood cells in adulthood
non-small cell lung cancer, a type of lung cancer
renal cell carcinoma
the thyroid cancer
the so-called gastrointestinal stroma tumor or GIST (a tumor of the gastrointestinal tract)
certain forms of breast cancer
Liver cell cancer and others.

At which stage of the disease the tyrosine kinase inhibitors are used, determines the disease and its course.

Active ingredient and effect

Tyrosine kinases are enzymes, i.e. key metabolic figures that are involved in the development and survival of malignant (malignant) tumors, cancer.
Uncontrolled activities of these enzymes in particular lead to the steady growth of cells from which malignant tumors can emerge. Tumor masses displace healthy tissue and spread degenerate cells in different ways, thus forming metastases in other organ systems.
In chronic myeloid leukemia in particular, the increased activity of the enzyme tyrosine kinase plays a decisive role in tumor development and spread.
Tyrosine kinase inhibitors inhibit the enzymes and thereby prevent the increased cell division of the diseased cells. In other cancers, too, some of the activity seems to be due to degenerate tyrosine kinases, which explains their effectiveness in treatment. In comparison to conventional anti-cancer drugs, so-called cytostatics, tyrosine kinase inhibitors have an even more targeted effect on sick cells and are therefore associated with comparatively fewer side effects. They belong to the range of active ingredients in so-called targeted cancer therapy and are genetically engineered as monoclonal antibodies. In this way, they act on a specific structure of the degenerate tumor cells.

For more information, see Tyrosine kinase.

The tyorsine kinase inhibitors are chemotherapeutic agents because of the way they work. There are other chemotherapy drugs available, including the cytostatics. If you would like to find out more, we recommend our website Chemotherapy substances

Side effects

Tyroine kinase inhibitors are very potent drugs. Its use can lead to side effects that do not necessarily occur in every patient. In some cases, these can be serious or even life-threatening, which is why a doctor should be consulted immediately.

When taking tyrosine kinase inhibitors, non-specific side effects are possible, such as loss of appetite, dizziness, hair loss, joint pain, indigestion, nausea, dry mouth, numbness or abnormal sensations, as well as numerous others. These side effects are to be expected to a certain extent, but if they occur to a large extent, a doctor should also be informed.
If you fear hair loss during chemotherapy, you should definitely read the following page: Accelerate hair growth after chemotherapy
Common side effects of treatment with tyrosine kinase inhibitors are increased water retention, edema and weight gain.
Infections can also occur more frequently, signs of which include fever, chills or sore throat. This is because the number of white blood cells decreases, which makes the immune system weak.
Bruising and bleeding can also occur as the blood clotting may be impaired.
In addition, the number of red blood cells may be reduced, which can be reflected in paleness, tiredness and shortness of breath.
Occasionally, during treatment with tyrosine kinase inhibitors, heart and lung problems, accompanied by chest pain, cough, or difficulty breathing, may occur.
Blood pressure can also be low, which can lead to dizziness or fainting.
Other side effects are skin problems
Other side effects are intestinal problems with nausea, diarrhea, vomiting or abdominal pain.
Serious side effects of the drug include liver damage, kidney damage, or muscle discomfort which may show up as urine discoloration, decreased urine output, or yellowing of the skin and sclera. If these side effects occur during treatment, a doctor should be informed immediately, as the side effects can be up to life-threatening.

In general, treatment with tyrosine kinase inhibitors requires close monitoring of symptoms and laboratory values. Patients should be fully informed about the therapy.

The tyrosine kinase inhibitors belong to the class of chemotherapeutic agents and, thanks to their targeted action, cause fewer side effects than the classic chemotherapeutic agents. If you are interested in the general side effects of chemotherapy, we recommend our website: Side effects of chemotherapy drugs

interaction

Tyrosine kinase inhibitors, like numerous other drugs, are metabolized and broken down by specific enzymes in the liver. Many drugs can influence the effect of tyrosine kinase inhibitors, on the other hand, tyrosine kinase inhibitors can also influence other active substances.The effect can be increased, which is associated with an increased risk of side effects; or decreased, which leads to a weakening of the effectiveness of cancer therapy.
Patients should inform the treating doctor about any medication they take, even if they are herbal medicines. St. John's wort, for example, which is used for mild to moderate depression, can accelerate the breakdown of tyrosine kinase inhibitors and weaken the effect. Other drugs that may interact with tyrosine kinase inhibitors include immune system suppressors, psychotropic drugs, epilepsy drugs, high blood pressure drugs, and cholesterol-lowering drugs. Other commonly used drugs such as paracetamol or blood thinners also lead to interactions when used at the same time. Patients should discuss additional medication with their doctor and pharmacist.

Tyrosine kinase inhibitors and alcohol - are they compatible?

Alcohol consumption is not strictly prohibited during treatment with tyrosine kinase inhibitors. Alcohol should be consumed in moderation, and you must continue to take the medication regularly. If vomiting or diarrhea occurs, the effectiveness of the tyrosine kinase inhibitor may be reduced.

Contraindications - When should a tyrosine kinase inhibitor not be used?

Tyrosine kinase inhibitors must not be taken if there is an allergy to the active substance or other components of the drug. Before taking it, the attending physician should be informed of any existing or past liver, kidney or heart diseases. A previous hepatitis B infection should also be examined, as this can reactivate the disease, which can be fatal. Patients taking the thyroid hormone preparation levothyroxine should also tell their doctor about it. Tyrosine kinase inhibitors can make these medicines less effective, so thyroid function should be checked regularly and the dose adjusted.

dosage

There is a large number of tyrosine kinase inhibitors that must be dosed differently depending on the indication and the patient. Patients should pay close attention to the instructions of their doctor or pharmacist, as correct intake is a prerequisite for the effectiveness of the drug. The usual dose in the treatment of chronic myeloid leukemia with the drug Glivec (contains the active ingredient imatinib, a tyrosine kinase inhibitor) is, for example, 400 or 600 mg once a day (4 or 6 capsules for capsules with 100 mg each).

price

Tyrosine kinase inhibitors are active ingredients from the group of genetically engineered monoclonal antibodies. This newer, targeted cancer treatment is still very expensive. As a rule, it is a long-term or even lifelong therapy to suppress a relapse. Glivec (contains the active ingredient imatinib) in the treatment of chronic myeloid leukemia costs over € 1,500 in a pack of 60 tablets with 100 mg of active ingredient per film-coated tablet.

Alternatives to tyrosine kinase inhibitors

In the treatment of chronic myeloid leukemia, the tyrosine kinase inhibitor imatinib belongs to the first-line therapy, especially when a certain genetic mutation is present. If the patient does not respond well to the medicine, the dose is initially doubled. Another option is the combination with interferon alpha. If the standard therapy is unsuccessful, stem cells from family donors or third-party donors are usually transplanted.
For other cancers, alternatives to immunotherapy with tyrosine kinase inhibitors are classic chemotherapy with various drugs, cytostatic drugs, or radiation therapy. The treatment regimen depends on the disease and individual factors.

If you are interested in classic chemotherapy as an alternative to tyrosine kinase inhibitors, please also read our page: Conducting chemotherapy

If you would like to find out more about stem cell transplantation as an alternative therapy for leukemia, we recommend our website: Stem cell transplant